Microsoft word - leverhaler laboratory white paper.doc

Laboratory White Paper
LeverHaler Valved Holding Chamber BirdSong Medical Devices, Inc. Brewster, New York Test: Laboratory: Thayer Labs, Tucson, AZ. Report: Albuterol Sulfate, Metaproterenol Sulfate 1.1 Comparative Product Testing Summary
Figure 1: Comparative Product Test Results:
Birdsong
Monaghan
Healthscan
Products
Dose Output Data
(•g proventil)
Dose Output Data (•g alupent)
1.2 Dose Output Testing with Proventil

To compare the total dose output (micrograms/dose) for the LeverHaler and two other devices. This is the total amount of active ingredient, summed over all particle sizes that would be delivered to a patient’s airways when the MDI canister is actuated properly, at the start of inhalation. MDI devices used
MDI drugs used
Proventil® HFA (albuterol sulfate)  Schering Test setup
Throat model feeds into filter. Harvard Breathing Machine inhales and exhales through filter, throat model, and MDI device. Active ingredient collected in filter is assayed by HPLC. MDI drug canister actuated at the start of inhalation of the Number of trials (n)
n = 10 (Total dose output measured ten times for each
Figure 2. (Schematic diagram) NOTE: The “MDI Chamber” represented in this
diagram refers to the Birdsong Medical LeverHaler Spacer Device. This is a generic
graphic provided by Thayer Labs and used in their standard test reports.
• MDI device feeds into USP standard aluminum throat model. • Filter is “Airlife Nonconductive Respiratory Therapy Filter, Bacterial/Viral • Harvard Breathing Machine inhales and exhales through filter, throat model, and MDI device. (Harvard Apparatus Dual Phase Control Respirator Pump, Harvard Apparatus, South Natick MA) • MDI drug canister is actuated at start of inhalation. • MDI drugs/boots used are Proventil HFA. • Active ingredient collected in the filter is assayed by HPLC.
Summary
This laboratory study compares the total mass of active ingredient delivered by the
LeverHaler and two devices (AeroChamber and OptiHaler), plus a throat model. The
result is a table of the average amount of drug (per spray) that would be delivered to a
patient who uses the device as directed. The results are also presented in graphical form.
For the MDI drug tested—Proventil HFA—the LeverHaler delivers at least as much total
active ingredient as the two predicate devices.
Method
• Three devices were compared, LeverHaler, AeroChamber and OptiHaler.
• The LeverHaler spacer device was used in ten trials (n = 10). • Ten different AeroChamber and ten different OptiHaler were used (n = 10). • Each device was used in a breathing simulation where the device was attached to a throat model and filter. The assembly was attached to a Harvard Breathing Machine, which was able to breathe through the assembly, subjecting the device to the same breathing patterns that a patient might exhibit. Any medication inhaled from the device would impact on the filter for analysis. • The breathing machine was set at 5 breaths per minute and a volume of 750 mL. • The MDI canister was actuated at the start of inhalation, as directed by the drug and • After delivery of the MDI doses, the filter was washed and analyzed (by HPLC) for dose output. For HPLC methods see the following section. • For each type of device, the average and standard deviation of the ten dose output • The Student t-test was used to compare dose output performance among the three • This procedure was carried out for the drug tested (Proventil HFA). Comments on chemical analysis for albuterol sulfate: • Centered on 350 nm; bandwidth 80 nm. • Phenomenex 150x4.60mm Luna 5µ c18(2). • 85% (0.05M KCl + 1% acetic acid) + 15% methanol. Figure 3: Comments on chemical analysis of albuterol sulfate (Proventil)

Results
The dose output results are summarized in the table, along with the p-values for t-tests
comparing each device with the two other devices. Any differences between devices are
considered to be statistically significant if p < 0.05.
Dose Output Data (µg albuterol sulfate)
LeverHaler
OptiHaler
AeroChamber
Dose Output (µg)
Dose output - Filter
micrograms albuterol 20
Figure 5: Graphical Dose Output Proventil
Conclusion
The LeverHaler was found to be statistically superior to the device OptiHaler when used
with Proventil HFA. The LeverHaler performs at least as well as the device
AeroChamber.

Note: Data accumulated for this Proventil Total Dose Output Test was obtained by
Thayer Labs actuating the MDI with the lever of the LeverHaler.
1.3 Dose Output Testing with Alupent

To compare the total dose output (micrograms/dose) for the LeverHaler and two devices. This is the total amount of active ingredient, summed over all particle sizes that would be delivered to a patient’s airways when the MDI canister is actuated properly, at the start of inhalation. MDI devices used
MDI drugs used
Alupent® ( metaproterenol sulfate )  Boehringer Ingelheim Test setup
Throat model feeds into filter. Harvard Breathing Machine inhales and exhales through filter, throat model, and MDI device. Active ingredient collected in filter is assayed by HPLC. MDI drug canister actuated at the start of inhalation of the Number of trials (n)
n = 10 (Total dose output measured ten times for each
Figure 6. (Schematic diagram) NOTE: The “MDI Chamber” noted in the diagram refers to the Birdsong
Medical LeverHaler Spacer. This graphic is a standard format used by Thayer Labs for this particular test
and is intended as a basic representation of the test.
• MDI device feeds into USP standard aluminum throat model. • Filter is “Airlife Nonconductive Respiratory Therapy Filter, Bacterial/Viral • Harvard Breathing Machine inhales and exhales through filter, throat model, and MDI device. (Harvard Apparatus Dual Phase Control Respirator Pump, Harvard Apparatus, South Natick MA) • MDI drug canister is actuated at start of inhalation. • Active ingredient collected in the filter is assayed by HPLC.
Summary
This laboratory study compares the total mass of active ingredient delivered by the
LeverHaler and two devices (AeroChamber and OptiHaler), plus a throat model. The
result is a table of the average amount of drug (per spray) that would be delivered to a
patient who uses the device as directed. The results are also presented in graphical form.
For the MDI drug tested—Alupent—the LeverHaler delivers at least as much total active
ingredient as the two devices.
Method
• Three devices were compared, LeverHaler, AeroChamber and OptiHaler.
• The LeverHaler was used in ten trials (n = 10). • Ten different AeroChambers and ten different OptiHaler were used (n = 10). • Each device was used in a breathing simulation where the device was attached to a throat model and filter. The assembly was attached to a Harvard Breathing Machine, which was able to breathe through the assembly, subjecting the device to the same breathing patterns that a patient might exhibit. Any medication inhaled from the device would impact on the filter for analysis. • The breathing machine was set at 5 breaths per minute and a volume of 750 mL. • The MDI canister was actuated at the start of inhalation, as directed by the drug and • After delivery of the MDI doses, the filter was washed and analyzed (by HPLC) for dose output. For HPLC methods see the following section. • For each type of device, the average and standard deviation of the ten dose output • The Student t-test was used to compare dose output performance among the three • This procedure was carried out for the three drug tested (Alupent). Comments on chemical analysis for metaproterenol sulfate: • Centered on 350 nm; bandwidth 80 nm. • Phenomenex 150x4.60mm Luna 5µ c18(2). • 85% (0.05M KCl + 1% acetic acid) + 15% methanol. Figure 7: Chemical analysis of metaproterenol sulfate

Results

The dose output results are summarized in the table, along with the p-values for t-tests
comparing each device with the two other devices. Any differences between devices are
considered to be statistically significant if p < 0.05.
Dose Output Data (µg metaproterenol sulfate)
LeverHaler
OptiHaler
AeroChamber
Dose Output (µg)
Figure 8: Dose Output Results: Alupent


Dose output - Filter
micrograms metaproterenal sulfate per
Figure 9: Graph of Dose Output: Alupent

Conclusion
The LeverHaler was found to be statistically superior to the device OptiHaler when used
with Alupent. The LeverHaler was found to be statistically equivalent to the
AeroChamber when used with Alupent.

Note: Data accumulated for this Alupent Total Dose Output Test was obtained by Thayer
Labs actuating the MDI with the lever of the LeverHaler

Source: http://oxlifeinc.hypermart.net/pdfs/LeverHaler%20Laboratory%20White%20Paper.pdf